Malignant mixed Müllerian tumors of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 44 cases.
OBJECTIVE
The authors retrospectively analyzed the prognostic significance of p53, mdm-2, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathologic factors in patients with malignant mixed Müllerian tumors (MMMT) of the uterus.


METHODS
Between 1970 and 1995, 44 uterine tumors were diagnosed as MMMT (21 stage I, 2 stage II, 10 stage III, and 11 stage IV). Thirty-two were homologous type and 12 were heterologous type. DNA flow cytometry and immunohistochemical analysis for p53 and mdm-2 overexpression were performed on paraffin-embedded archival tissue.


RESULTS
68% of the tumors were nondiploid and 61% had an SPF greater than 10%. Sixty-one percent overexpressed p53 and 25% were mdm-2-positive. Furthermore, 91% of the tumors had a mitotic count greater than 10/10 hpf and 95% had high-grade cytologic atypia. Twenty-seven (61%) patients died of tumor and 6 (14%) died of intercurrent disease. Eleven (25%) patients are alive with no evidence of disease. The median follow-up for patients still alive was 59 months (range, 28-178 months). The overall 5-year survival rate was 38%. In a univariate analysis that included stage, histologic type, DNA ploidy, SPF, p53, mdm-2, mitotic index, and age, and with survival as the end point, only stage reached statistically prognostic significance.


CONCLUSIONS
The majority of the tumors had obvious signs of aggressiveness such as high grade, high mitotic count, nondiploid pattern, high SPF, and overexpression of p53. This study found that stage is the most important prognostic factor for survival in MMMTs of the uterus.
Blom
R
R
Department of Gynecological Oncology, University Hospital, Linköping, Sweden.
Guerrieri
C
C
Stâl
O
O
Malmström
H
H
Sullivan
S
S
Simonsen
E
E
D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D008940:Mitotic Index; D018200:Mixed Tumor, Mullerian / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D011003:Ploidies; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012189:Retrospective Studies; D016196:S Phase; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics; D014594:Uterine Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2